UHPLC-MS/MS bioanalysis of human plasma coproporphyrins as potential biomarkers for organic anion-transporting polypeptide-mediated drug interactions

Bioanalysis
Hamza KandoussiRenuka Pillutla

Abstract

Coproporphyrins (CP-I and CP-III) have been identified as possible biomarkers to predict human hepatic organic anion-transporting polypeptides-mediated-drug-interactions for a new drug entering clinical development. The method is applicable to quantify plasma CP-I and CP-III within 0.078-15.0 nM. The results identify and address a number of challenges encountered with porphyrin assays such as photodegradation and interferences. To overcome interferences from ubiquitous porphyrins, a surrogate matrix was used to prepare calibration standards. Quality controls were prepared in plasma and surrogate matrix to ensure parallelism between surrogate matrix and plasma. A robust UHPLC-MS/MS assay was developed and validated for CP-I and CP-III in plasma, and is currently applied to clinical studies to confirm suitability of Coproporphyrins as a potential substitute for drug-drug interaction study.

References

Jan 1, 1985·Advances in Experimental Medicine and Biology·J MoanA Western
Feb 26, 2016·The Journal of Pharmacology and Experimental Therapeutics·Hong ShenYurong Lai

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Citations

Jul 30, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yueping ZhangHong Shen

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